Standard chemotherapy for advanced small cell lung cancer (“SCLC”) has not changed substantially in the last two decades. The challenge when identifying novel SCLC therapies is the prevalence of inactivating mutations in tumor suppressor genes (TP53, PTEN, RBI), and only infrequent gain-offunction mutations in oncogenes such as PIK3CA or MYC family members. Inhibitors of bromodomain and extraterminal (BET)-bromodomain (BRD) proteins can modulate the transcription of oncogenes, such as the MYC family, via inhibition ofBRD binding to acetylated lysines on histone proteins, preventing the assembly of transcriptional coregulators on target gene promoters.
The compound of Formula (1), described herein below, has been shown to inhibit the binding of acetylated histone H4 to the tandem bromodomain (BRD)-containing family of transcriptional regulators known as the BET (bromodomains and extraterminal) proteins, which include BRD2, BRD3, and BRD4. See U.S. Patent Application Publication No. 2010/0286127 A1, which is incorporated herein by reference in its entirety. The BET proteins have emerged as major epigenetic regulators of proliferation and differentiation and also have been associated with predisposition to dyslipidemia or improper regulation of adipogenesis, elevated inflammatory profile and risk for cardiovascular disease and type 2 diabetes, and increased susceptibility to autoimmine diseases such as rheumatoid arthritis and systemic lupus erythematosus as reported by Denis, G. V. “Bromodomain coactivators in cancer, obesity, type 2 diabetes, and inflammation,” Discov Med 2010; 10:489-499, which is incorporated herein by reference in its entirety. Accordingly, the compound of formula (1) may be useful for treatment of various cancers, cardiovascular disease, type 2 diabetes, and autoimmune disorders such as rheumatoid arthritis and systemic lupus erythematosus.